Task-specific Disruptions in Theta Oscillations during Working Memory for Temporal Order in People with Schizophrenia.

Prior studies demonstrated that neural oscillations are enhanced during working memory (WM) maintenance and that this activity can predict behavioral performance in healthy individuals. However, it is unclear whether the relationship holds for people with WM deficits. People with schizophrenia have marked WM deficits, and such deficits are most prominent when patients are required to process relationships between items, such as temporal order. Here, we used EEG to compare the relationship between oscillatory activity and WM performance in patients and controls. EEG was recorded as participants performed tasks requiring maintenance of complex objects ("Item") or the temporal order of objects ("Order"). In addition to testing for group differences, we examined individual differences in EEG power and WM performance across groups. Behavioral results demonstrated that patients showed impaired performance on both Item and Order trials. EEG analyses revealed that patients showed an overall reduction in alpha power, but the relationship between alpha activity and performance was preserved. In contrast, patients showed a reduction in theta power specific to Order trials, and theta power could predict performance on Order trials in controls, but not in patients. These findings demonstrate that WM impairments in patients may reflect two different processes: a general deficit in alpha oscillations and a specific deficit in theta oscillations when temporal order information must be maintained. At a broader level, the results highlight the value of characterizing brain-behavior relationships, by demonstrating that the relationship between neural oscillations and WM performance can be fundamentally disrupted in those with WM deficits.

Memory-Based Prediction Deficits and Dorsolateral Prefrontal Dysfunction in Schizophrenia.

BACKGROUND: Theories suggest that people with schizophrenia (SZ) have problems generating predictions based on past experiences. The dorsolateral prefrontal cortex (DLPFC) and hippocampus participate in memory-based prediction. We used functional magnetic resonance imaging to investigate DLPFC and hippocampal function in healthy control (HC) subjects and people with SZ during memory-based prediction. METHODS: Prior to scanning, HC subjects (n = 54) and people with SZ (n = 31) learned 5-object sequences presented in fixed or random orders on each repetition. During scanning, participants made semantic decisions (e.g., "Can this object fit in a shoebox?") on a continuous stream of objects from fixed and random sequences. Sequence prediction was demonstrated by faster semantic decisions for objects in fixed versus random sequences because memory could be used to anticipate and more efficiently process semantic information about upcoming objects in fixed sequences. Representational similarity analyses were used to determine how each sequence type was represented in the posterior hippocampus and DLPFC. RESULTS: Sequence predictions were reduced in individuals with SZ relative to HC subjects. Representational similarity analyses revealed stronger memory-based predictions in the DLPFC of HC subjects than people with SZ, and DLPFC representations correlated with more successful predictions in HC subjects only. For the posterior hippocampus, voxel pattern similarity was increased for fixed versus random sequences in HC subjects only, but no significant between-group differences or correlations with prediction success were observed. CONCLUSIONS: Individuals with SZ are capable of learning temporal sequences; however, they are impaired using memory to predict upcoming events as efficiently as HC subjects. This deficit appears related to disrupted neural representation of sequence information in the DLPFC.

Disrupted Modulation of Alpha and Low Beta Oscillations Mediates Temporal Sequence Memory Deficits in People With Schizophrenia.

BACKGROUND: People with schizophrenia (SZ) exhibit impaired episodic memory when relating objects to each other in time and space. Empirical studies and computational models suggest that low-frequency neural oscillations may be a mechanism by which the brain keeps track of temporal relationships during encoding and retrieval, with modulation of oscillatory power as sequences are learned. It is unclear whether sequence memory deficits in SZ are associated with altered neural oscillations. METHODS: Using electroencephalography, this study examined neural oscillations in 51 healthy control subjects and 37 people with SZ during a temporal sequence learning task. Multiple 5-object picture sequences were presented across 4 study-test blocks in either fixed or random order. Participants answered semantic questions for each object (e.g., living/nonliving), and sequence memory was operationalized as faster responses for fixed versus random sequences. Differences in oscillatory power between fixed versus random sequences provided a neural index of temporal sequence memory. RESULTS: Although both groups showed reaction time differences in late blocks (blocks 3 and 4), this evidence of sequence memory was reduced in people with SZ relative to healthy control subjects. Decreases in globally distributed prestimulus alpha (8-12 Hz) and beta 1 (13-20 Hz) power for fixed versus random sequences in late blocks were also attenuated in people with SZ relative to healthy control subjects. Moreover, changes in oscillatory power predicted individual reaction time differences and fully mediated the relationship between group and sequence memory. CONCLUSIONS: Disrupted modulation of alpha and beta 1 electroencephalography oscillations is a candidate mechanism of temporal sequence memory deficits in people with SZ.

Disruption of the anterior thalamic head direction signal following reduction of the hippocampal theta rhythm.

There is overlap between the structures containing head direction (HD) cells and those mediating the hippocampal theta rhythm, and both signals are thought to play an important role in spatial navigation. Previous research has shown that reversible inactivation of the medial septum attenuates hippocampal theta activity and disrupts path integration-based navigation. Although the HD signal reflects navigational performance, it is unclear whether theta rhythm contributes to the direction-specific activity of HD cells. We sought to determine whether HD cell activity is changed following reversible inactivation of the medial septum to eliminate theta rhythm. HD cells were recorded from the anterodorsal thalamus of female Long-Evans rats while they navigated in a cylindrical environment across standard, landmark rotation, and dark conditions. Following infusions of muscimol into the medial septum, recordings demonstrated a clear decrease in the power of hippocampal theta oscillations. In the landmark rotation experiment, intraseptal administration of muscimol produced HD cells with preferred directions that shifted unpredictably between sessions, suggesting that cue control was affected. Further, following septal inactivation many HD cells were unable to maintain a stable preferred firing direction within the recording sessions when the animals locomoted in the dark, suggesting that idiothetic processing was affected. These findings provide evidence that theta oscillations contribute to the directional stability of HD cells in anterodorsal thalamus. (PsycInfo Database Record (c) 2021 APA, all rights reserved).